AL amyloidosis is a rare but devastating complication of multiple myeloma that can rapidly lead to heart and kidney failure. In this disease, abnormal plasma cells produce defective antibody fragments that misfold and build up as toxic amyloid deposits in vital organs. Even when current therapies successfully slow or stop production of these harmful proteins, the existing amyloid remains in the body and continues to damage organs. For patients with advanced disease, survival is often measured in months, highlighting the urgent need for therapies that can actively remove amyloid deposits.
Dr. Lentzsch’s project builds on earlier work that led to the development of anselamimab, one of the first antibodies designed to bind directly to AL amyloid and help immune cells clear it from the body. While promising, this treatment benefited only patients with one subtype of the disease, known as kappa (κ) amyloidosis. Unfortunately, about 80% of patients have the lambda (λ) form, leaving most patients without an effective option.
She and her team have identified key reasons why amyloid clearance has been difficult and developed a new approach called Bispecific Phagocyte Engagers (BiPEs). These engineered molecules are designed to directly connect amyloid deposits with the immune cells responsible for removing harmful material from the body, allowing for more efficient clearance even in the presence of normal antibodies in the bloodstream.
They will now extend this strategy to the much more common λ form of AL amyloidosis. If successful, this work could lead to first-in-human clinical testing for the majority of AL amyloidosis patients and open the door to new treatments for other protein-aggregation diseases as well.
Project and Grants
Bispecific phagocyte engagers for AL amyloidosis precise immunotherapy
